Lipid lowering and beyond: results from the CARE study on lipoproteins and inflammation. Cholesterol and Recurrent Events

Abstract

The plasma LDL concentration in firmly established as a cause of coronary heart disease. However, the efficacy of LDL lowering may reach a limit when it is brought well below average during treatment. The Cholesterol and Recurrent Events (CARE) trial compared pravastatin and placebo in patients who had experienced myocardial infarction who had average concentrations of total cholesterol < 240 mg/dl (baseline mean 209 mg/dl) and LDL cholesterol (LDL) 115 to 174 mg/dl (mean 139 mg/dl). Pravastatin reduced coronary death or recurrent myocardial infarction by 24%. In multivariate analysis, the LDL concentration achieved during follow-up was a significant predictor of the coronary event rate. The relationship was nonlinear since the coronary event rate declined as LDL decreased during follow-up from 174 to approximately 125 mg/dl, but no further decline was seen in the LDL range from 125 to 71 mg/dl. A major ongoing effort in the CARE trial concerns the identification of non-LDL mediated mechanisms of coronary events. Chronic low-grade inflammation has recently been identified as an important new risk factor for coronary artery disease. Two markers of inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), were measured in patients in the CARE trial who suffered a recurrent myocardial infarction or coronary death and in those who did not have these recurrent events. Levels of both inflammatory markers were significantly higher among post-myocardial infarction patients who subsequently developed recurrent coronary events. This association was significant in the patients who were treated with placebo but not in those in the pravastatin group. In conclusion, attaining an LDL of < 125 mg/dl may be sufficient treatment of LDL concentrations, removing the adverse effect of LDL on coronary events. These findings also raise the possibility that the efficacy of pravastatin may partly result from anti-inflammatory as well as lipid lowering properties.